An observational, multicenter study. There will be different cohorts, every TKI will be assessed separately. (erlotinib, gefitinib, afatinib, osimertinib, crizotinib, ceritinib, alectinib). For every TKI there is a WBRT (N=10) and a SRT (N=10) cohort

Standardized neurocognitive examination will be done before radiotherapy, after 4 months and after 6 months. A magnetic resonance imaging (MRI) of the brain will be performed at 4 and at 6 months (partly already usual care). Optionally cerebrospinal fluid (CSF) will be obtained by lumbar puncture before and two weeks after radiotherapy. Optionally blood will be obtained by venipuncture before and two weeks after radiotherapy

Incidence of acute severe toxicity (per TKI) 2 weeks after completion of cranial radiotherapy

Incidence of neurotoxicity 4 months after completion of cranial radiotherapy compared to baseline data

Stage IV NSCLC with driver mutation, treated with TKI

Development of brain metastases during TKI treatment

Indication for cranial radiotherapy determined by treating physician and radiation oncologist with continuation of the TKI

Age ≥ 18 years

Ability to understand neurocognitive testing

Written informed consent

Prior radiotherapy to the brain when this precludes new radiotherapy.

Neurologic/psychiatric illnesses (such as Alzheimer*s disease)

Claustrophobia

Metal implants or other contra-indication for MRI

Inability to lie supine for 30 minutes time (MRI)