Yes, if the aircraft is in the “away” state you can on guard them.
No matter the settings they have set, once the pilot stops touching their device for two minutes straight their status will be set to “away” to indicate that they may be away from their device.
We don’t expect controllers to wait till the pilot is confirmed to be at their device to send them a on guard. That proactive on guard can be used to get them on the controller’s frequency when they’re able.
We don’t expect the pilot to always be at their device in non-critical phases of flight, like at cruise, even when they are on an ATC frequency, like if they were with Center.