# Brain metastases (secondary brain tumours)

Source: https://onco.cc/cancers/secondary-brain-tumours/  
OnCo record `secondary-brain-tumours` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Brain metastases are cancers that have spread to the brain from elsewhere, most often from the lung, breast or skin. Focused radiation aimed at each spot (radiosurgery) has largely replaced radiation to the whole brain, and for some cancers modern targeted drugs and immunotherapy reach the brain well enough to shrink the deposits on their own.

## Summary

Brain metastases seed the grey-white junction and watershed zones through the arterial circulation; they are recognised on contrast MRI and, with a known primary, rarely need biopsy. Prognosis depends on the primary, its molecular subtype, performance status, extracranial disease and number of lesions (graded prognostic assessment). Dexamethasone relieves oedema. Management has moved in twenty years from whole-brain radiotherapy for nearly everyone to a choice among surgery, stereotactic radiosurgery, systemic therapy with brain penetration and, for some, no brain-directed treatment at all.

Surgery is used for a large or symptomatic single lesion or when tissue is needed (Patchell, 1990), followed by radiosurgery to the cavity rather than whole-brain radiotherapy (N107C, 2017). For a limited number of metastases, Alliance N0574 (JAMA 2016) showed that adding whole-brain radiotherapy to radiosurgery worsened cognition at three months in 91.7 percent of patients against 63.5 percent with radiosurgery alone, without lengthening survival, and radiosurgery alone is now standard for up to four lesions and increasingly for more. When whole-brain radiotherapy is still used, NRG CC001 (JCO 2020) showed hippocampal avoidance with memantine preserves cognition. QUARTZ (Lancet 2016) found no meaningful gain in quality-adjusted survival from whole-brain radiotherapy in non-small cell lung cancer patients unsuited to surgery or radiosurgery, so best supportive care alone is legitimate in poor-prognosis patients.

Systemic therapy now controls brain disease in several subtypes: osimertinib in EGFR-mutant and lorlatinib in ALK-positive lung cancer (CROWN), tucatinib with trastuzumab and capecitabine (HER2CLIMB) and trastuzumab deruxtecan (DESTINY-Breast12) in HER2-positive breast cancer, nivolumab plus ipilimumab in melanoma (CheckMate 204) and dabrafenib plus trametinib in BRAF-mutant melanoma (COMBI-MB), so asymptomatic small metastases in these groups are often treated with drugs first and radiosurgery held in reserve. Trials have historically excluded patients with brain metastases; their inclusion, the management of leptomeningeal disease, radionecrosis after radiosurgery, and drugs designed to cross the blood-brain barrier are the open fronts.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Brain metastases; Secondary brain cancer; Intracranial metastases; Cerebral metastases; Brain mets
- Tags: subtype-page; cns
- Group: central nervous system
- Burden: The commonest intracranial tumour in adults, many times more frequent than primary brain tumours; lung cancer, breast cancer, melanoma, kidney cancer and bowel cancer account for most, and incidence is rising as people live longer with systemic disease.
- Subtypes: Brain metastases from non-small cell lung cancer (EGFR, ALK and other driver subsets); Brain metastases from breast cancer (HER2-positive, triple-negative); Brain metastases from melanoma; Brain metastases from kidney, bowel and other cancers; Solitary brain metastasis (surgical candidate); Multiple brain metastases (radiosurgery or whole-brain radiotherapy); Leptomeningeal metastases (cerebrospinal fluid spread)
- Biomarkers: Primary tumour type and its driver (EGFR, ALK, HER2, BRAF, PD-L1); Number, size and location of lesions on contrast MRI; Graded prognostic assessment (age, performance status, extracranial disease, lesion count, molecular subtype); Cerebrospinal fluid cytology and cell-free DNA for leptomeningeal disease; Distinguishing radionecrosis from progression (perfusion MRI, amino acid PET)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/secondary-brain-tumours/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/secondary-brain-tumours/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/secondary-brain-tumours/#what-it-is [7 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/secondary-brain-tumours/#finding-it [5 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/secondary-brain-tumours/#treating-it [7 settings, 4 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/secondary-brain-tumours/#evidence [15 trials, 4 key papers, 10 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/secondary-brain-tumours/#science [6 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/secondary-brain-tumours/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/secondary-brain-tumours/#living-with-it [24 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/secondary-brain-tumours/coming/ [10 medicines, 15 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/secondary-brain-tumours/data/ [61 connected records]

## Standard of care

- Symptomatic oedema: Dexamethasone, tapered as quickly as symptoms allow; anticonvulsants only after a seizure. ([Dexamethasone](https://onco.cc/drugs/dexamethasone/))
- Single large or symptomatic lesion, fit patient: Surgical resection followed by radiosurgery to the cavity (N107C) rather than whole-brain radiotherapy. ([Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)](https://onco.cc/technologies/radiosurgery-srs/))
- Limited number of metastases: Stereotactic radiosurgery alone (Alliance N0574); whole-brain radiotherapy withheld because it worsens cognition without lengthening life. ([Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)](https://onco.cc/technologies/radiosurgery-srs/), [Gamma Knife](https://onco.cc/technologies/gamma-knife/), [CyberKnife robotic radiosurgery](https://onco.cc/technologies/cyberknife/), [Alliance N0574 (NCCTG N0574)](https://onco.cc/trials/alliance-n0574/))
- Many metastases or leptomeningeal spread: Hippocampal-avoidance whole-brain radiotherapy with memantine (NRG CC001) where whole-brain treatment is chosen; radiosurgery to many lesions in selected patients; best supportive care alone in poor-prognosis lung cancer (QUARTZ). ([Whole-brain radiotherapy (WBRT)](https://onco.cc/terms/wbrt/), [NRG CC001](https://onco.cc/trials/nrg-cc001/), [QUARTZ](https://onco.cc/trials/quartz/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/))
- Driver-positive lung cancer, asymptomatic metastases: Brain-penetrant targeted therapy first: osimertinib (EGFR), lorlatinib or alectinib (ALK); radiosurgery for progression. ([Osimertinib](https://onco.cc/drugs/osimertinib/), [Lorlatinib](https://onco.cc/drugs/lorlatinib/), [Alectinib](https://onco.cc/drugs/alectinib/), [CROWN](https://onco.cc/trials/crown/))
- HER2-positive breast cancer: Tucatinib with trastuzumab and capecitabine (HER2CLIMB) or trastuzumab deruxtecan (DESTINY-Breast12), with local therapy for symptomatic lesions. ([Tucatinib](https://onco.cc/drugs/tucatinib/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [HER2CLIMB](https://onco.cc/trials/her2climb/), [DESTINY-Breast12](https://onco.cc/trials/destiny-breast12/))
- Melanoma: Nivolumab plus ipilimumab for asymptomatic metastases (CheckMate 204); dabrafenib plus trametinib for BRAF V600-mutant disease (COMBI-MB); radiosurgery for symptomatic or progressing lesions. ([Nivolumab](https://onco.cc/drugs/nivolumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)](https://onco.cc/technologies/radiosurgery-srs/))

## State of the art

- Radiosurgery alone has replaced whole-brain radiotherapy for limited disease because it spares cognition without costing survival.
- Several targeted drugs and immunotherapy doublets now control brain metastases well enough to be used before radiation.
- Whole-brain radiotherapy, once universal, is now reserved for extensive disease and given with hippocampal avoidance and memantine.

## Open problems

- Trials still often exclude patients with brain metastases, so drug activity in the brain is learned late.
- Leptomeningeal disease has no standard treatment and a survival of months.
- Radionecrosis after radiosurgery is hard to tell from progression and hard to treat.
- Few drugs are designed from the start to cross the blood-brain barrier.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Brain_metastasis
- Wikipedia: https://en.wikipedia.org/wiki/Brain_metastasis
- Alliance N0574: radiosurgery with or without whole-brain radiotherapy (JAMA 2016): https://doi.org/10.1001/jama.2016.9839
- QUARTZ (Lancet 2016): https://doi.org/10.1016/S0140-6736(16)30825-X

## Connected records

- cancers: [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [BRAF V600-mutant melanoma](https://onco.cc/cancers/braf-v600-melanoma/), [Brain and spinal cord tumours (all types)](https://onco.cc/cancers/brain-tumours/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [HER2-positive breast cancer with brain metastases](https://onco.cc/cancers/her2-positive-breast-brain-metastases/), [Melanoma](https://onco.cc/cancers/melanoma/), [Meningioma](https://onco.cc/cancers/meningioma/), [Metastatic cancer (cancer that has spread)](https://onco.cc/cancers/metastatic-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Spinal cord tumours (intramedullary and intradural)](https://onco.cc/cancers/spinal-cord-tumours/)
- technologies: [CyberKnife robotic radiosurgery](https://onco.cc/technologies/cyberknife/), [Focused-ultrasound blood-brain barrier opening](https://onco.cc/technologies/bbb-focused-ultrasound/), [Gamma Knife](https://onco.cc/technologies/gamma-knife/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [MRI](https://onco.cc/technologies/mri/), [Stereotactic radiosurgery (Gamma Knife, CyberKnife, linac SRS)](https://onco.cc/technologies/radiosurgery-srs/)
- drugs: [Alectinib](https://onco.cc/drugs/alectinib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Dexamethasone](https://onco.cc/drugs/dexamethasone/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Lorlatinib](https://onco.cc/drugs/lorlatinib/), [Memantine](https://onco.cc/drugs/memantine/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Osimertinib](https://onco.cc/drugs/osimertinib/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [Tucatinib](https://onco.cc/drugs/tucatinib/)
- terms: [Blood-brain barrier (BBB)](https://onco.cc/terms/blood-brain-barrier/), [Brain metastases (intracranial disease)](https://onco.cc/terms/brain-metastases/), [Graded Prognostic Assessment (GPA) for brain metastases](https://onco.cc/terms/graded-prognostic-assessment/), [HER2-positive brain metastases](https://onco.cc/terms/her2-brain-metastases/), [Leptomeningeal disease](https://onco.cc/terms/leptomeningeal-disease/), [Stereotactic radiosurgery (SRS)](https://onco.cc/terms/stereotactic-radiosurgery/), [Whole-brain radiotherapy (WBRT)](https://onco.cc/terms/wbrt/)
- trials: [A Pivotal Phase II Clinical Trial of Utidelone Injection Plus Capecitabine in HER2-negative Breast Cancer Patients With Brain Metastases](https://onco.cc/trials/nct06764940/), [Alliance N0574 (NCCTG N0574)](https://onco.cc/trials/alliance-n0574/), [CheckMate 204](https://onco.cc/trials/checkmate-204/), [CROWN](https://onco.cc/trials/crown/), [DESTINY-Breast12](https://onco.cc/trials/destiny-breast12/), [Efficacy and Safety of SPH4336 in Combination With Endocrine Therapy in Breast Cancer Patients With Brain Metastases.](https://onco.cc/trials/nct05872347/), [HER2CLIMB](https://onco.cc/trials/her2climb/), [JROSG 99-1 (Aoyama): stereotactic radiosurgery with or without whole-brain radiotherapy](https://onco.cc/trials/jrosg-99-1/), [NRG CC001](https://onco.cc/trials/nrg-cc001/), [Phase 2b Imaging Study of RAD101 in Participants With Suspected Recurrent Brain Metastases](https://onco.cc/trials/nct06777433/), [Phase II Study of Gamma Knife Radiosurgery and Temozolomide for Brain Metastases](https://onco.cc/trials/nct00582075/), [QUARTZ](https://onco.cc/trials/quartz/), [Study of Abemaciclib and Elacestrant in Participants With Brain Metastasis Due to ER+/HER-2- Breast Cancer](https://onco.cc/trials/nct05386108/), [Study to Establish the Diagnostic Performance of 18F Fluciclovine PET in Detecting Recurrent Brain Metastases](https://onco.cc/trials/nct04410133/), [TY-9591 in the Patients With EGFR Mutations in Advanced NSCLC With Brain Metastases](https://onco.cc/trials/nct05948813/)
- key papers: [Alliance N0574: radiosurgery alone versus radiosurgery plus whole-brain radiotherapy for one to three brain metastases](https://onco.cc/key-papers/paper-alliance-n0574-brown-jama-2016/), [N107C/CEC.3: postoperative radiosurgery versus whole-brain radiotherapy after resection of a brain metastasis](https://onco.cc/key-papers/paper-n107c-brown-lancet-oncol-2017/), [NRG CC001: hippocampal-avoidance whole-brain radiotherapy plus memantine for brain metastases](https://onco.cc/key-papers/paper-nrg-cc001-brown-jco-2020/), [QUARTZ: whole-brain radiotherapy versus supportive care alone for brain metastases from non-small-cell lung cancer](https://onco.cc/key-papers/paper-quartz-lancet-2016/)
- people: [Paul D. Brown](https://onco.cc/people/paul-brown/)

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JSON: https://onco.cc/api/v1/entities/secondary-brain-tumours.json