Prospective phase III, multicentre randomised (1:1) open label superiority study

Study of stereotactic radiosurgery, in addition to standard systemic therapy for patients with metastatic melanoma or newly diagnosed metastatic NSCLC and asymptomatic or oligo-symptomatic brain metastases. Immunotherapy or targeted therapy with or without stereotactic radiosurgery for patients with brain metastases from melanoma or non-small cell lung cancer

Newly diagnosed, previously untreated (except for surgery, see below) asymptomatic or oligo-symptomatic brain metastases, e.g., controlled symptomatic seizure disorder. Note: patients with neurological symptoms or signs that require more than a stable dose of 4 mg dexamethasone equivalent for more than one week are not considered oligo-symptomatic.

Number and size of metastases at diagnosis of brain metastases (as per Yamamoto et al.)[2]: - Maximum 1-10 brain metastases - At least one brain metastasis must be of ≥5 mm in diameter

Confirmed or probable leptomeningeal metastasis according to EANO ESMO criteria [12]

Symptomatic brain metastases at time of randomisation, e.g., neurological symptoms or signs that require more than a stable dose of 4 mg dexamethasone equivalent for more than one week.

• Patients must be off steroids or on a stable dose of ≤4 mg dexamethasone equivalent for one week prior to randomisation.