A Randomized Phase II Study Evaluating Upfront SRT to All Brain Metastases Followed by Ivonescimab Plus Chemotherapy Versus Upfront Ivonescimab Plus Chemotherapy in Patients With Asymptomatic Active Brain Metastases From NSCLC

Inclusion Criteria: * Age 18 years or older * ECOG PS \<= 2 * Patients with pathology proven metastatic NSCLC without an actionable genomic alteration for which there is first line targeted treatment approved by EMA and recommended by the ESMO guidelines. * Asymptomatic or clinically symptomatic brain metastases defined as requiring a dose of steroids of maximum 4 mg equivalent dexamethasone per day for the last 7 days to control neurological symptoms. With the clinically oligosymptomatic further defined as having no indication for immediate localized brain therapy, including neurosurgery or radiotherapy. Patients with controlled seizures can be enrolled. * Newly diagnosed brain metastasis with the following characteristics: * 1-10 newly diagnosed and untreated (except resected) brain metastases Note: if the neuronavigation MRI in the upfront SRS/FSRT arms shows \> 10 metastases, but the MRI used for enrolment showed 1-10 metastases, the patient will be still considered eligible. * At least one metastasis should be at least 5x5 mm. In case of doubt on the diagnosis of brain metastasis, the lesion should not be irradiated but followed up. * The largest metastasis must be \<10 mL in volume and \<30 mm in longest diameter (resected lesions would not count). * The maximum cumulative volume of brain metastases must be \<30 mL (resected lesions would not count) * Adequate Organ Function Exclusion Criteria: * Patients with oligometastatic NSCLC who are scheduled to recei…